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TAK-243 preferentially bound to UBA1 above the associated E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 reduced levels of ubiquitylated proteins, improved markers of proteotoxic worry and DNA hurt worry. In vivo, TAK-243 decreased leukemic load and specific leukemic stem cells with no proof of toxicity. Ultima